Conventional protein kinase C in the brain: repurposing cancer drugs for neurodegenerative treatment?

Q4 Neuroscience Neuronal signaling Pub Date : 2021-10-08 eCollection Date: 2021-12-01 DOI:10.1042/NS20210036
Gema Lordén, Alexandra C Newton
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Abstract

Protein Kinase C (PKC) isozymes are tightly regulated kinases that transduce a myriad of signals from receptor-mediated hydrolysis of membrane phospholipids. They play an important role in brain physiology, and dysregulation of PKC activity is associated with neurodegeneration. Gain-of-function mutations in PKCα are associated with Alzheimer's disease (AD) and mutations in PKCγ cause spinocerebellar ataxia (SCA) type 14 (SCA14). This article presents an overview of the role of the conventional PKCα and PKCγ in neurodegeneration and proposes repurposing PKC inhibitors, which failed in clinical trials for cancer, for the treatment of neurodegenerative diseases.

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脑中的常规蛋白激酶 C:重新利用抗癌药物治疗神经退行性疾病?
蛋白激酶 C(PKC)同工酶是一种受到严格调控的激酶,可从受体介导的膜磷脂水解中传递大量信号。它们在大脑生理过程中发挥着重要作用,PKC 活性失调与神经退行性病变有关。PKCα 的功能增益突变与阿尔茨海默病(AD)有关,而 PKCγ 的突变会导致脊髓小脑共济失调(SCA)14 型(SCA14)。本文概述了传统 PKCα 和 PKCγ 在神经退行性疾病中的作用,并建议将在癌症临床试验中失败的 PKC 抑制剂重新用于治疗神经退行性疾病。
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CiteScore
4.60
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0.00%
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审稿时长
14 weeks
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